• Gustavo da Fontoura Galvão, Elielson Veloso da Silva, Fabrícia Lima Fontes-Dantas, Ricardo Castro Filho, Soniza Alves-Leon, and Marcondes de Souza Jorge J Federal University of Rio de Janeiro, University Hospital Clementino Fraga Filho, Department of de Neurosurgery, Rio de Janeiro RJ, Brazil. Ele.
• Federal University of Rio de Janeiro, University Hospital Clementino Fraga Filho, Department of de Neurosurgery, Rio de Janeiro RJ, Brazil; Federal University of the State of Rio de Janeiro, Translational Neuroscience Laboratory, Post-Graduation Program in Neurology, Rio de Janeiro RJ, Brazil.
• World Neurosurg. 2020 Oct 1; 142: 481-486.e1.

BackgroundFamilial cerebral cavernous malformations (CCM) are among the most common vascular malformations of the central nervous system (CNS) and are linked to mutations on the specific genes CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. We present the first report in the literature of a pharmaco-resistant epileptic patient harboring co-occurring pathogenic mutations within CCM2/MGC4607 and CCM1/KRIT1.Case DescriptionA 51-year-old patient first presented at age of 33 years with episodes of seizures. Magnetic resonance imaging including a susceptibility-weighted imaging sequence had shown multiple cerebral cavernous malformation lesions. She had partial response of symptoms and remained in routine follow-up needing progressive pharmacological improvement. Direct sequencing allowed the detection of 1 nonsense pathogenic mutation in CCM2/MGC4607 (c.118C>T; p.Arg40Ter) and 1 unclassified frameshift insertion variant in CCM1/KRIT1 (c.1687_1688insT; p.Tyr563LeufsTer5).ConclusionsAlthough the CCM2/MGC460 variant seems to be the major contributor for the patient's CCM phenotype, the mutated CCM1/KRIT1 seems to act as a booster to CCM overall pathogenicity.Copyright © 2020. Published by Elsevier Inc.

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